Malignant Heme Flashcards
Subsequent Line Treatment of CML with acquired T315l mutation
Ponatinib + Asciminib
- Panatinib more arterial occlusive events
(less commonly used: Omacetaxine)
Used in patients with myelofibrosis and severe thrombocytopenia
Pacritinib
Induction regimen of choice for patients with treatment related AML and chromosome 5,7 deletions
Liopsomal doxorubicin + cytarabine
Treatment of newly diagnosed AML:
a. without drive mutation
b. with FLT3 mutation
c. with IDH1/2 mutation
CMV prophylaxis after transplant:
- 1st Line
- 2nd Line
1st Line- Letermovir
2nd Line- Maribavir
GELF Criteria for FL
GELF Criteria for High Tumor Burden in Follicular Lymphoma
1. Nodal or extranodal masses ≥ 7 cm in diameter
- Any single lymph node or extranodal mass that is 7 cm or larger.
2. Three or more nodal sites, each ≥ 3 cm
- Presence of three or more lymph nodes, each at least 3 cm in size.
3. B symptoms
4. Splenomegaly
5. Pleural effusions or ascites
6. Leukemia phase: Circulating lymphoma cells (leukemic involvement) with an ALC ≥ 5 x 10⁹/L.
7. Cytopenias: Hemoglobin level < 10 g/dL, or platelet count < 100 x 10⁹/L due to bone marrow involvement.
Treatment of relapsed/refractory DLBCL with ECOG 0-1
IF MORE THAN 12 MONTHS SINCE RELAPSE: CHEMO SENSITIVE
1. Salvage chemotherapy (2-3 cycles) followed by restating PET and if response, proceed with high dose chemotherapy and ASCT.
Common salvage chemotherapy regimens include:
- R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin)
- R-ICE (rituximab, ifosfamide, carboplatin, etoposide)
- R-GDP (rituximab, gemcitabine, dexamethasone, cisplatin)
If they achieve a sufficient response (usually complete or partial remission), they proceed to high-dose chemotherapy followed by ASCT.
IF MORE THAN 12 MONTHS: PRIMARY REFRACTORY/EARLY RELAPSE
- CAR-T cell therapy preferred with axicabtagene ciloleucel or lisocabtagene maraleucel
Common Positive CD Markers for B cell disorders
a. CLL
b. Mantle Cell
c. Marginal Zone
d. Follicular
a. CLL: (+) CD5, CD19, CD23
b. Mantle Cell: (+) CD5, CD19, CD20
c. Marginal Zone: (+) CD11c, CD19, CD20
d. Follicular: (+) CD10, CD19, CD20
Treatment of CLL without TP53 mutation/17p deletion (category 1)
a. First Line (4)
b. Second Line (2)
c. Relapse after first line therapy if period of clinical remission
a. First Line:
- Acalabrutinib +/- obinutuzumab
- Venetoclax +/- obinutuzumab
- Ibruitinib
- Zanibrutinib
b. Second Line:
- BTKi (Acala/Zanu-bruitinib)
- BCL2 inhibitor: venetoclax + rituxumab
C. Re-treatment with Venetoclax +/- obinutuzumab
Treatment of CLL WITH TP53 mutation/17p deletion
a. First Line (3)
b. Second Line (3)
First Line:
* Acalabrutinib ± obinutuzumab
* Venetoclax + obinutuzumab
* Zanubrutinib
Second Line:
* Acalabrutinib
* Venetoclax + rituximab
* Zanubrutinib
4th Line Therapy options for multiple myeloma (6)
–Selinexor + Dexamethasone [for patients refractory to 2 PIs, at least two IMiDs and anti-CD38 antibody]
–Idecabtagene vicleucel [Preferred]
–Ciltacabtagene autoleucel [Preferred]
–Teclistamab-cqyv [Preferred]
–Talquetamab-tgvs [Preferred]
–Elranatamab-bcmm [Preferred]
Treatment of multiple myeloma with Anti-CD38 Refractory disease (2)
– Carfilzomib/lenalidomide/dexamethasone (category 1)
– Pomalidomide/bortezomib/dexamethasone (category 1)
Treatment of multiple myeloma with Bortezomib-Refractory disease (4)
–Carfilzomib/lenalidomide/dexamethasone (category 1)
–Daratumumab/carfilzomib/dexamethasone (category 1)
– Daratumumab/lenalidomide/dexamethasone (category 1)
– Isatuximab-irfc/carfilzomib/dexamethasone (category 1)
Treatment of multiple myeloma with Lenalidomide-Refractory disease (4)
– Daratumumab/bortezomib/dexamethasone (category 1)
– Daratumumab/carfilzomib/dexamethasone (category 1)
– Isatuximab-irfc/carfilzomib/dexamethasone (category 1)
– Pomalidomide/bortezomib/dexamethasone (category 1)
Gene rearrangement associated with follicular lymphoma
Follicular lymphoma is associated with t(14;18). This translocation juxtaposes BCL2 found on chromosome 18 to IgH found on chromosome 14. BCL2 has anti-apoptotic activity
Burkitt’s Lymphoma/Leukemia:
- CD markers
- Ki67
- Additional testing that is positive
CD45+
B cell markers (CD19, CD22 and CD79a) are all positive
Monoclonal light chain expression of kappa or lambda is positive
CD10+, CD38+, CD43+, CD71+ and bcl-6+
The blast markers CD34 and TdT are negative
Usually Bcl-2−, CD43+
Additional testing reveals expression of PAX-5 (B cell marker) and the Ki-67 (proliferation marker) is expected to be strongly positive. Many cases are EBER (EBV) positive.
T lymphoid markers
CD3+, CD5+, CD7+, CD1a+, CD2+, CD4+, CD8+
TCR+, CD10+
TdT+
B lymphoid markers
CD19+, CD10+, CD20+, CD22+, CD24+, cCD79a+
Tdt+ (Moderate to Bright), cyIgM+
AML CD markers
cMPO+, CD13+, CD33+, CD65+, CD14+, CD15+, CD64+, CD117+
CD33+ Favorable Risk AML induction regimen and dosing
Standard-dose cytarabine 200 mg/m2 CI x 7 days + Daunorubicin 60 mg/m2 x 3 days &
1 single dose of Gemtuzumab Ozogamicin 3 mg/m2 (up to one 4.5 mg vial) on day 1, 2, 3 or 4
Treatment of FLT3 mutated AML:
a. First Line
b. Relapsed/Refractory
a. First Line:
Standard dose cytarabine 200 mg/m2 CI x 7 days + Daunorubicin 60 mg/m2 x 3 days (or Idarubicin) & oral midostaurin 50 mg every 12 hours, days 8-21.
b. Relapsed/refractory AML with FLT3 ITD mutation:
–Gilteritinib
–Hypomethylating agent + Sorafenib
–Quizartinib
Favorable Risk AML genetic abnormalities
t(8;21)(q22.q22.1)
Inv(16) or t(16;16)
Mutated NPM1 without FLT3-ITD
Biallelic mutated CEBPA [bZIP in-frame mutated CEBPA]
Intermediate Risk AML genetic abnormalities
Mutated NPM1 and FLT3-ITD
Wild-type NPM1 with FLT3-ITD [without adverse-risk genetic lesions]
t(9;11)(p21.3;q23.3)
Cytogenetic abnormalities not classified as favorable or adverse
Treatment of refractory FLT3 mutated AML and associated AE
Gilteritinib
Adverse Side Effects:
1. Posterior reversible encephalopathy syndrome (PRES)
2. Prolonged QT Interval:
- Interrupt and reduce Gilteritinib in patients who have a QTcF >500 msec
- Correct hypokalemia or hypomagnesemia prior to and during administration.
3. Pancreatitis
Maintinance therapy for FLT3 AML and associated indications
For patients with AML with FLT3 mutation, the three different consolidation treatment regimens include
–Cytarabine + Midostaurin (FLT3-ITD or TKD)
–Cytarabine + Quizartinib (FLT3-ITD only)
–Allogeneic HCT
If an Allogeneic transplant is performed and a patient with FLT3 mutated AML is in remission, then a FLT3 inhibitor as maintenance therapy should be recommended.
Options include:
–Sorafenib (FLT3-ITD only)
–Midostaurin (FLT3-ITD or TKD; Category 2B)
–Gilteritinib (FLT3-ITD or TKD; Catgeory 2B)
–Quizartinib (FLT3-ITD only)
First Line treatment of plasma cell leukemia for fit patients
Frontline Treatment of mantle cell lymphoma
a. Aggressive treatment regimens (2)
b. Less-aggressive treatment regimens (4)
a. Aggressive Treatment Regimens/TP53 mutated:
–Zanubrutinib/Obinutuzumab/Venetoclax
–TRIANGLE regimen with Covalent Bruton’s tyrosine kinase inhibitor + Rituximab
b. Non-aggressive Treatment Regimens/ Non-TP53 mutated
–Rituximab, Dexamethasone, Cytarabine + Platinum (Carboplatin, Oxaliplatin or Cisplatin) x 4 cycles followed
by R-CHOP for non-PET CR
–Alternating R-CHOP + Covalent BTK inhibitor/R-DHA + Platinum
–NORDIC regimen (Dose-intensified induction immunochemotherapy with Rituximab + Cyclophosphamide,
Vincristine, Doxorubicin, Prednisone alternating with Rituximab + High-dose cytarabine)
–Rituximab + Bendamustine followed by Rituximab/High-dose Cytarabine
AML favorable risk
– t(8;21)
– Inv(16) or t(16;16)
– Mutated NPM1 without FLT3-ITD
– bZIP in-frame mutated CEBPA
AML intermediate risk
– Mutated NPM1 with FLT3-ITD
– Wild-type NPM1 with FLT3-ITD
– t(9;11)
AML high risk
t(6;9)(p23;q34.1)/DEK::NUP214
t(v;11q23.3)/KMT2A rearranged (excluding KMT2A-PTD)
t(9;22)(q34.1;q11.2)/BCR::ABL1
(8;16)(p11;p13)/KAT6A::CREBBP
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2, MECOM(EVI1)
t(3q26.2;v)/MECOM(EVI1)-rearranged
−5 or del(5q); −7; −17/abn(17p)
Complex karyotype (change in definition)e; Monosomal Karyotype
Mutated ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, or ZRSR2f
Mutated TP53 (Variant Allele Frequency ≥10%)
AML with FLT3 mutation:
First Line + associated AE
Second Line + associated AE
First Line- AraC + Midosaurin (AE: nausea, GI)
Second Line
– Gliteritinib (AE: PRES, QTC prolongation, pancreatitis)
– Quizartinib (AE: WBC, QTC prolongation)
AML with IDH1/2 mutations
IDH1 mutation:
AZA 75 mg/m2 qD SC/IV d1-7 (alternatively d1-5 + d8-9) + Ivosidenib 500 mg PO QD d1-28
– If unable to tolerate chemotherapy, can be treated with Ivosidenib mono therapy
IDH2: Enasidenib: 100 mg PO QD d1-28, q4 weeks, until disease progression
2nd Line/Treatment of relapsed/refractory mantle cell lymphoma
Covalent BTKis (acalabrutinib and zanubrutinib) and lenalidomide + rituximab
Mantle cell lymphoma typical immunophenotype
- positive stain if unclear diagnosis?
- FISH if unclear diagnosis
Immunophenotype:
CD5+, CD20+, CD43+, cyclin D1+, CD10-/+
Stain: Cyclin D1
FISH: t (11, 14 )
